Ischemia is a feature of heart, kidney, liver, and intestinal diseases, transient ischemic attacks, cerebrovascular accidents, ruptured arteriovenous malformations, and peripheral artery occlusive disease. In contrast to hypoxia, which is a more general term denoting a shortage of oxygen (usually a result of lack of oxygen in the air being breathed), ischemia is an absolute or relative shortage of the blood supply to an organ. Relative shortage means the mismatch of blood supply (oxygen delivery) and blood request for adequate oxygenation of tissue. Ischemia can also be described as an inadequate flow of blood to a part of the body, caused by constriction or blockage of the blood vessels supplying it. Since oxygen is mainly bound to hemoglobin in red blood cells, insufficient blood supply causes tissue to become hypoxic, or, if no oxygen is supplied at all, anoxic. This can cause necrosis (i.e. cell death).
Tissues especially sensitive to inadequate blood supply are the heart, liver, kidneys, and brain. Ischemia in brain tissue, for example due to stroke or head injury, causes a process called the ischemic cascade to be unleashed, in which proteolytic enzymes, reactive oxygen species, and other harmful chemicals damage and may ultimately kill brain tissue.
Restoration of blood flow after a period of ischemia can actually be more damaging than the ischemia. Reintroduction of oxygen causes a greater production of damaging free radicals, resulting in reperfusion injury. With reperfusion injury, necrosis can be greatly accelerated.
Disclosed herein are compositions and methods to stimulate repair and regeneration of injured tissue, such as tissue damaged from ischemia. For example, the disclosed compositions and methods are efficacious in the treatment of acute brain injury due to stroke, spinal cord injury due to compression, acute cardiac injury due to ischemia, and acute liver or kidney injury due to drug or toxicant exposure or ischemia.